This application is for a Program Project grant to support the research program of the Division of Clinical Research. It includes a series of integrated projects on the general theme of susceptibility and response of humans to oncogenic agents. There is evidence that the infectious agent associated with Australia antigen (Au, HAA, HbAg, etc.) has oncogenic properties, or is related to similar agents which are oncogenic. We propose to study the properties of Au as a prototype of an oncogenic agent which is different in character from a typical virus. We hope that additional knowledge about Au will allow us to identify other agents similar to it which are involved in the etiology and pathogenesis of cancer, in particular hepatoma and childhood leukemia. Au appears to interact with genetically determined attributes of humans, and the genetic constitution of the human host may determine the nature of his response. There is also a striking maternal effect. Therefore, a study of Au, and the hypothesized related agents, requires a concurrent study of host reactions. The program includes studies on the epidemiology, immunology and genetics of hepatoma, Au and alpha-fetoprotein; the parents of patients with leukemia compared to parents of normal children; a series of studies on maternal effects of Au; chemical, biological and immunologic characteristics of Au; and the investigation of "new" precipitins found in the serum of transfused patients. In addition, there is an investigation of the characteristics of agents related to the tubercle bacillus (but not BCG) which may be of practical value in the immunotherapy of cancer.